Total Cerebral Small Vessel Disease Research Articles

Association of pulsatility index with total burden of cerebral small vessel disease and cognitive impairment.

This study investigated the correlation between the pulsatility index (PI) of the middle cerebral artery with the total burden of cerebral small vessel disease and cognitive impairment. Information on patients hospitalized in the Department of Neurology was collected retrospectively. These patients had complete clinical and laboratory data. The middle cerebral artery PI was measured using transcranial Doppler, a Mini-Mental State Examination (MMSE) was used to assess cognitive function, and the total cerebral small vessel disease burden was assessed using magnetic resonance imaging. Patients were grouped according to their scores for total imaging burden of cerebral small vessel disease and cognitive function. Logistic regression analysis assessed the association between the PI, total imaging burden, and cognitive impairment. Spearman analysis was used to evaluate the correlation between the PI and total imaging burden and cognitive impairment, and receiver operating characteristic (ROC) curves were used to determine the predictive value of the PI for cognitive function. The PI was higher in the cognitive impairment (CI) group than in the no-CI group. Binary logistic regression analysis showed that increased PI was an independent risk factor for CI (OR=1.582; 95% CI: 1.043-2.401; p=.031) and total imaging burden (OR=1.842; 95% CI: 1.274-2.663; p=.001). Spearman analysis found that the PI correlated negatively with the MMSE score (r=-.627, p<.001). ROC curve analysis showed the PI predicted CI with an area under the curve of 0.784. The PI combined with the total imaging burden predicted CI in cerebral small vessel disease with an area under the curve of 0.832. An increased PI was associated with CI and a high imaging burden in cerebral small vessel disease patients. The PI combined with the total burden score shows a high predictive value for CI.

Total cerebral small vessel disease burden and stroke outcomes in large vessel occlusion stroke receiving endovascular treatment: A systematic review and meta-analysis

BackgroundCerebral small vessel disease (CSVD) is prevalent in the population, especially among the elderly. Various types of CSVD markers commonly coexist, and the neurological function outcome is affected by their combined effect. Studies investigating the association between total CSVD burden and stroke outcomes in large vessel occlusion (LVO) stroke receiving endovascular treatment (EVT) are expanding but have not been systematically assessed. MethodsWe systematically searched the PubMed, Embase, and Cochrane databases for relevant clinical studies. The total CSVD burden score summarized the markers of CSVD, including lacunes, white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVSs), which was a comprehensive index of overall CSVD burden. The pooled odds ratios (ORs) were used to calculate the association between high total CSVD burden score and outcomes of EVT in patients with LVO stroke. The primary outcome was poor functional outcome, which was defined as a modified Rankin Scale score (mRS) ≥ 3 at 90 days after EVT. The secondary outcomes were symptomatic intracranial hemorrhage (sICH) and poor collateral flow. ResultsOverall, 6 eligible studies with 1,774 patients with LVO stroke undergoing EVT were pooled in meta-analysis. High overall CSVD burden score was significantly associated with increased risks of poor functional outcome at 90 days (pooled OR 2.86, 95 % CI 1.31–6.25, p = 0.008). Besides, high overall CSVD burden score was associated with sICH (pooled OR 2.07, 95 % CI 0.38–5.17; p = 0.118) and poor collateral flow (pooled OR 1.57, 95 % CI 0.75–3.27; p = 0.232), but were not statistically significant. ConclusionsHigh overall CSVD burden was associated with increased risks of unfavorable outcomes in patients with LVO stroke undergoing EVT.

A Nomogram Including Total Cerebral Small Vessel Disease Burden Score for Predicting Mild Vascular Cognitive Impairment in Patients with Type 2 Diabetes Mellitus.

Total cerebral small vessel disease (CSVD) burden score is an important predictor of vascular cognitive impairment (VCI). However, few predictive models of VCI in type 2 diabetes mellitus (T2DM) patients have included the total CSVD burden score, especially in the early stage of VCI. To develop and validate a nomogram that includes the total CSVD burden score to predict mild VCI in patients with T2DM. A total of 322 eligible participants with T2DM who were divided into mild and normal cognitive groups were enrolled in this retrospective study. Demographic data, laboratory data and imaging markers of CSVD were collected. The total CSVD burden score was calculated by combining the different CSVD markers. Step-backward multivariable logistic regression analysis with the Akaike information criterion was applied to select significant predictors and develop a best-fit predictive nomogram. The performance of the nomogram was assessed in terms of discriminative ability, calibrated ability, and clinical usefulness. The nomogram model consisted of five variables: age, education, hemoglobin A1c level, serum homocysteine level, and total CSVD burden score. A nomogram with these variables showed good discriminative ability (area under the receiver operating characteristic curve was 0.801 in internal verification). In addition, the Hosmer-Lemeshow test (χ2 =9.226, P=0.417) and bootstrap-corrected calibration plot indicated that the nomogram had good calibration. The Brier score of the predictive model was 0.178. Decision curve analysis demonstrated that when the threshold probability ranged between 16% and 98%, the use of the nomogram to predict mild VCI in patients with T2DM provide a greater net benefit. The nomogram, composed of age, education, stroke, HbA1c level, Hcy level, and total CSVD burden score, had good predictive accuracy and may provide clinicians with a practical tool for predicting the risk of mild VCI in T2DM patients.

Quantitative Analysis of Multimodal MRI Markers and Clinical Risk Factors for Cerebral Small Vessel Disease Based on Deep Learning.

Cerebral small vessel disease lacks specific clinical manifestations, and extraction of valuable features from multimodal images is expected to improve its diagnostic accuracy. In this study, we used deep learning techniques to segment cerebral small vessel disease imaging markers in multimodal magnetic resonance images and analyze them with clinical risk factors. We recruited 211 lacunar stroke patients and 83 control patients. The patients' cerebral small vessel disease markers were automatically segmented using a V-shaped bottleneck network, and the number and volume were calculated after manual correction. The segmentation results of the V-shaped bottleneck network for white matter hyperintensity and recent small subcortical infarction were in high agreement with the ground truth (DSC>0.90). In small lesion segmentation, cerebral microbleed (average recall=0.778; average precision=0.758) and perivascular spaces (average recall=0.953; average precision=0.923) were superior to lacunar infarct (average recall=0.339; average precision=0.432) in recall and precision. Binary logistic regression analysis showed that age, systolic blood pressure, and total cerebral small vessel disease load score were independent risk factors for lacunar stroke (P<0.05). Ordered logistic regression analysis showed age was positively correlated with cerebral small vessel disease load score and total cholesterol was negatively correlated with cerebral small vessel disease score (P<0.05). Lacunar stroke patients exhibited higher cerebral small vessel disease imaging markers, and age, systolic blood pressure, and total cerebral small vessel disease score were independent risk factors for lacunar stroke patients. V-shaped bottleneck network segmentation network based on multimodal deep learning can segment and quantify various cerebral small vessel disease lesions to some extent.

An Integrative Nomogram for Identifying Cognitive Impairment Using Seizure Type and Cerebral Small Vessel Disease Neuroimaging Markers in Patients with Late-Onset Epilepsy of Unknown Origin.

Cognitive impairment (CI) is a common comorbidity in patients with late-onset epilepsy of unknown origin (LOEU). However, limited data are available on effective screening methods for CI at an early stage. We aimed to develop and internally validate a nomogram for identifying patients with LOEU at risk of CI and investigate the potential moderating effect of education on the relationship between periventricular white matter hyperintensities (PVHs) and cognitive function. We retrospectively reviewed the clinical data of 61 patients aged ≥ 55years diagnosed with LOEU. The main outcome was CI, reflected as an adjusted Montreal Cognition Assessment score of < 26 points. A nomogram based on a multivariable logistic regression model was constructed. Its discriminative ability, calibration, and clinical applicability were tested using calibration plots, the area under the curve (AUC), and decision curves. Internal model validation was conducted using the bootstrap method. The moderating effect of education on the relationship between PVH and cognitive function was examined using hierarchical linear regression. Forty-four of 61 (72.1%) patients had CI. A nomogram incorporating seizure type, total cerebral small vessel disease burden score, and PVH score was built to identify the risk factors for CI. The AUC of the model was 0.881 (95% confidence interval: 0.771-0.994) and 0.78 (95% confidence interval: 0.75-0.8) after internal validation. Higher educational levels blunted the negative impact of PVH on cognitive function. Our nomogram provides a convenient tool for identifying patients with LOEU who are at risk of CI. Moreover, our findings demonstrate the importance of education for these patients.

P.059 Cerebral small vessel disease burden as a predictor of longitudinal cognition in patients with transient ischemic attack

Background: Cerebral small vessel disease (CSVD) is associated with stroke, cognitive decline, and dementia. In this study, we examined how SVD is longitudinally related to cognitive performance in transient ischemic attack (TIA) patients compared to controls. Methods: We rated CSVD at baseline on MRI in TIA patients (n=197) and controls (n=113) for microbleeds (CMB), lacunes, white matter hyperintensities (WMH), and perivascular spaces (EPVS). Neuropsychological testing was administered across 5 years using the following assessments: BVMT, RAVLT, TMTA, TMTB, WAIS-R. Results: Periventricular WMH≥2 yielded slower performance on TMTB across all timepoints (adjusted difference 20.3 seconds, 95%CI [8.4,32.2]), as did deep WMH≥2 (20.1 sec, 95%CI [7.6,32.6]). Basal ganglia EPVS&gt;20 performed slower on TMTA (10.1 sec, 95%CI [4.7,15.5]) and TMTB (21.2 sec, 95%CI [3.4,39.1]). Centrum semiovale EPVS&gt;20 performed slower on TMTB (27.2 sec, 95%CI [10.6,43.8]) and worse on WAIS-R at 5-years (-18.6, 95%CI [-35.0,-2.2]). Lacunes≥3 performed slower on TMTA across all timepoints (4.0 sec, 95%CI [0.1,7.9]). Total CSVD≥2 performed slower on TMTA (3.7 sec, 95%CI [0.4,7.0]) and TMTB (13.9 sec, 95%CI [2.9,24.9]) across 5 years. When stratifying results, associations were generally found in TIA, not controls. Conclusions: Findings demonstrate that CSVD is associated with poorer cognitive performance longitudinally, and is more pronounced in TIA compared to control.

Total Cerebral Small Vessel Disease Burden Predicts the Outcome of Acute Stroke Patients after Intra-Arterial Thrombectomy

Introduction: Various types of cerebral small vessel diseases (cSVD) markers commonly coexist. The neurological function outcome is affected by their combined effect. To investigate the effect of cSVD on intra-arterial thrombectomy (IAT), our study aimed at developing and testing a model with fusing a combination of multiple cSVD markers as total cSVD burden to predict the outcome of acute ischemic stroke (AIS) patients after IAT treatment. Methods: From October 2018 to March 2021, continuous AIS patients with IAT treatment were enrolled. We calculated the cSVD markers identified by magnetic resonance imaging. The outcomes of all patients were assessed according to the modified Rankin Scale (mRS) score at 90 days after stroke. The relationship between total cSVD burden and outcomes was analyzed by logistics regression analysis. Results: A total of 271 AIS patients were included in this study. The proportions of score 0∼4 in the total cSVD burden group (i.e., score 0, 1, 2, 3, and 4 groups) were 9.6%, 19.9%, 23.6%, 32.8%, and 14.0%, respectively. The higher the cSVD score, the more patients with a poor outcome. Heavier total cSVD burden (1.6 [1.01∼2.27]), diabetes mellitus (1.27 [0.28∼2.23]), and higher national institute of health stroke scale (NIHSS) on admission (0.15 [0.07∼0.23]) were associated with poor outcome. In the two Least Absolute Shrinkage and Selection Operator regression models, model 1 using age, duration from onset to reperfusion, Alberta stroke program early CT score (ASPECTS), NIHSS on admission, modified thrombolysis in cerebral infarction (mTICI) and total cSVD burden as variables perform well on predicting short-term outcome in area under curve (AUC) of 0.90. Model 2, including all of the variables above except cSVD, showed less predictive capability than model 1 (AUC 0.90 vs. 0.82, p = 0.045). Conclusions: The total cSVD burden score was independently associated with the clinical outcomes of AIS patients after IAT treatment and it may be a reliable predictor for poor outcomes of AIS patients after IAT treatment.

Association between total cerebral small vessel disease score and cognitive function in patients with vascular risk factors.

Hypertension is the most important risk factor for cerebral small vessel disease (SVD). In this cross-sectional study, we tested the independent association of cerebral SVD burden with global cognitive function and each cognitive domain in patients with vascular risk factors. The Tokyo Women's Medical University Cerebral Vessel Disease (TWMU CVD) registry is an ongoing prospective, observational registry in which patients with any evidence of CVD in magnetic resonance imaging (MRI) and at least one vascular risk factor were consecutively enrolled. For SVD-related findings, we evaluated white matter hyperintensity, lacunar infarction, cerebral microbleeds, enlarged perivascular space, and medial temporal atrophy. We used the total SVD score as the SVD burden. They underwent the Mini-mental State Examination (MMSE) and Japanese version of the Montreal Cognitive Assessment (MoCA-J) global cognitive tests, and each cognitive domain was evaluated. After excluding patients without MRI T2* images and those with MMSE score <24, we analyzed 648 patients. The total SVD score was significantly associated with MMSE and MoCA-J scores. After adjustment for age, sex, education, risk factors, and medial temporal atrophy, the association between the total SVD score and MoCA-J score remained significant. The total SVD score was independently associated with attention. In conclusion, the total SVD score, cerebral SVD burden, was independently association with global cognitive function and attention. A strategy to reduce SVD burden will have the potential to prevent cognitive decline. A total of 648 patients with any evidence of cerebral small vessel disease (SVD) in MRI and at least one vascular risk factor underwent Mini-mental State Examination (MMSE) and Japanese version of the Montreal Cognitive Assessment (MoCA-J) global cognitive tests. The total SVD scores count the presence of each SVD-related findings (white matter hyperintensity, Lacunar infarction, cerebral microbleeds and enlarged perivascular space), ranging from 0 to 4, as the SVD burden. Total SVD scores were significantly associated with MoCA-J scores (r = -0.203, P < 0.001). After adjustment for age, sex, education, risk factors, and medial temporal atrophy, the association between the total SVD score and global cognitive scores remained significant.

Abstract P671: Association Between Renal Function and Silent Cerebrovascular Disease in Japanese Men

Background and Aim: To determine whether a mild decrease in renal function is an indicator of early detection of silent cerebrovascular disease, we conducted a cross-sectional study in 735 community-dwelling Japanese men. Methods: The prevalence of silent cerebrovascular disease was defined as intracranial artery stenosis (ICAS), lacunar infarctions (LIs), cerebral microbleeds (CMBs), periventricular hyperintensities (PVHs: grade ≥2), and deep and subcortical white matter hyperintensities (DSWMHs: grade ≥3), using brain magnetic resonance imaging independently evaluated by two specialists. In addition, a total cerebral small vessel disease (TCSVD) score was used, summing LIs, CMBs, PVHs, and DSWMHs. We calculated the estimated glomerular filtration rate calculated with creatinine or cystatin C (eGFRcr or eGFRcys) using the CKD-EPI formula for Japanese and the equations by the Japanese Society of Nephrology, respectively. The urinary albumin/creatinine ratio (UACR) was dichotomized at 30 mg/gCre, and the low group was further divided into tertiles. eGFRcr and eGFRcys were also dichotomized at 60 ml/min/1.73 m 2 , and the high group was further divided into tertiles. The odds ratios (ORs) and 95% confidence intervals (95%CIs) for the prevalence of silent cerebrovascular disease by renal function were calculated using binary or ordinal multivariable adjusted logistic regression models. Results: The prevalence of ICAS, LIs, CMBs, and white matter lesions (WMLs: the prevalence of PVHs or DSWMHs) was 30% (220/735), 21% (155/735), 14% (102/735), and 32% (237/735), respectively. The multivariable adjusted ORs (95%CI) of the prevalence of CMBs and TCSVD score were higher in the high UACR (&gt;30mg/gCre) group (3.83 (1.90-7.73) and 1.75 (1.12-2.74), respectively) than in the low UACR (≤4.7 mg/gCre) group; the linear trend was significant (p &lt;0.001 and p=0.025, respectively). The multivariable adjusted ORs (95%CI) of TCSVD score was higher in the decreased (&lt;60 ml/min/1.73 m 2 ) eGFRcr or eGFRcys group (1.70 (0.998-2.91) and 1.85 (1.10-3.10), respectively) than in the high eGFRcr group (≥75.9 ml/min/1.73 m 2 ) or the high eGFRcys group (≥83.3 ml/min/1.73 m 2 ); the linear trend was shown (p=0.036 and p=0.072, respectively). The multivariable adjusted ORs (95%CI) of the prevalence of WML was higher in the decreased (&lt;60 ml/min/1.73 m 2 ) and mildly decreased (60-69.9 ml/min/1.73 m 2 ) eGFRcr groups (2.41 (1.31-4.43) and 1.78 (1.05-3.02), respectively) than in the high eGFRcr group (≥75.9 ml/min/1.73 m 2 ); the linear trend was significant (p&lt;0.001). eGFRcys and the prevalence of WML also showed similar associations. Conclusion: Decreased renal function was associated with the presence of silent cerebrovascular disease. Our results suggest that even a mild decline in renal function may be an indicator of early detection of silent cerebrovascular disease.

Impact of total cerebral small vessel disease score on ophthalmic artery morphologies and hemodynamics

BackgroundCerebral small vessel disease (CSVD) is a systemic disease, affecting not only the brain, but also eyes and other organs. The total CSVD score is a tool for comprehensive evaluation of brain lesions in patients with CSVD. The ophthalmic artery (OA) is a direct response to ocular blood flow. However, little is known about the correlation between CSVD and characteristics of OA. We investigated the OA morphologies and hemodynamics in patients with CSVD and the correlation between these changes and the total CSVD score.MethodsThis cross-sectional observational study included 34 eyes from 22 patients with CSVD and 10 eyes from 5 healthy controls. The total CSVD score was rated according to the CSVD signs on magnetic resonance imaging. OA morphological characteristics were measured on the basis of 3D OA model reconstruction. OA hemodynamic information was calculated using computational fluid dynamics simulations.ResultsThe total CSVD score negatively correlated with the OA diameter, blood flow velocity, and mass flow ratio (all P < 0.05). After adjusting for potential confounding factors, the total CSVD score was still independently correlated with the OA blood velocity (β = − 0.202, P = 0.005). The total CSVD score was not correlated with OA angle (P > 0.05). The presence of cerebral microbleeds and enlarged perivascular spaces was correlated with the OA diameter (both P < 0.01), while the lacunar infarcts and white matter hyperintensities were correlated with the OA blood velocity (both P < 0.001).ConclusionsThe decrease of the blood velocity in the OA was associated with the increase in the total CSVD score. The changes of the OA diameter and velocity were associated with the presence of various CSVD signs. The findings suggest that more studies are needed in the future to evaluate CSVD by observing the morphologies and hemodynamics of OA.

Systemic Immune-Inflammation Index is Associated with Cerebral Small Vessel Disease Burden and Cognitive Impairment.

This study sought to explore the associations of the systemic immune-inflammation index (SII) with total cerebral small vessel disease (CSVD) burden and cognitive impairment. We enrolled 201 patients in the retrospective study with complete clinical and laboratory data. The SII was calculated as platelet count × neutrophil count/lymphocyte count. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Total CSVD burden was assessed based on magnetic resonance imaging. We performed logistic regression models, Spearman correlation, and mediation analysis to evaluate the associations of SII with CSVD burden and cognitive impairment. After adjustment for confounding factors in the multivariate binary logistic regression model, elevated SII (odds ratio [OR], 3.263; 95% confidence interval [CI], 1.577-6.752; P = 0.001) or severe CSVD burden (OR, 2.794; 95% CI, 1.342-5.817; P = 0.006) was significantly associated with the risk of cognitive impairment. Correlation analyses revealed that SII levels were negatively associated with MMSE scores (rs = -0.391, P < 0.001), and positively associated with the total CSVD burden score (rs = 0.361, P < 0.001). Moreover, SII was significantly related to the severity of the CSVD burden (OR, 2.674; 95% CI, 1.359-5.263; P = 0.004). The multivariable-adjusted odds ratios (95% CI) in highest tertile versus lowest tertile of SII were 8.947 (3.315-24.145) for cognitive impairment and 4.945 (2.063-11.854) for severe CSVD burden, respectively. The effect of higher SII on cognitive impairment development was partly mediated by severe CSVD burden. Elevated SII is associated with severe CSVD burden and cognitive impairment. The mediating role of severe CSVD burden suggests that higher SII may contribute to cognitive impairment through aggravating CSVD burden.

A new nomogram including total cerebral small vessel disease burden for individualized prediction of early-onset depression in patients with acute ischemic stroke.

ObjectivesThe present study was designed to evaluate the effects of total cerebral small vessel disease (CSVD) on early-onset depression after acute ischemic stroke (AIS), and to develop a new nomogram including total CSVD burden to predict early-onset post-stroke depression (PSD).MethodsWe continuously enrolled patients with AIS who were hospitalized at the First Affiliated Hospital of Soochow University between October 2017 and June 2019. All patients were assessed for depressive symptoms using the 17-item Hamilton Depression Scale (HAMD-17) at 14 ± 2 days after the onset of AIS. The diagnosis for depression was made according to the American Diagnostic and Statistical Manual of Mental Disorders Version 5 (DSM-5). The demographic and clinical data were collected including total CSVD burden. On the basis of a multivariate logistic model, the independent factors of early-onset PSD were identified and the predictive nomogram was generated. The performance of the nomogram was evaluated by Harrell's concordance index (C-index) and calibration plot.ResultsA total of 346 patients were enrolled. When contrasted to a 0 score of total CSVD burden, the score ≥2 (moderate to severe total CSVD burden) was an independent risk factor for early-onset PSD. Besides, gender, cognitive impairments, baseline Barthel Index (BI), and plasma fibrinogen were independently associated with early-onset PSD. The nomogram based on all these five independent risk factors was developed and validated with an Area Under Curve (AUC) of 0.780. In addition, the calibration plot revealed an adequate fit of the nomogram in predicting the risk of early-onset depression in patients with AIS.ConclusionsOur study found the total CSVD burden score of 2–4 points was an independent risk factor of early-onset PSD. The proposed nomogram based on total CSVD burden, gender, cognitive impairments, baseline BI, and plasma fibrinogen concentration gave rise to a more accurate and more comprehensive prediction for early-onset PSD.

Risk factors and predictive scoring system for twice or more strokes in patients with cerebral small vessel disease

Objectives To explore the independent risk factors of twice or more strokes in patients with cerebral small vessel disease, and to construct a predictive scoring system. Methods A retrospective study was carried out in Tangshan, Hebei Province, China. Patients with cerebral small vessel disease suffered from acute stroke and admitted to Neurology Department of Tangshan Gongren Hospital from January 2020 to June 2021 were collected and grouped according to whether they had a previous stroke history. Binary logistic regression models were used to investigate the independent risks for the occurrence of twice or more strokes in patients with cerebral small vessel disease, assigned scores to each factor, then established and evaluated the predictive efficacy of the predictive scoring system. Results A total of 531 patients were included. Regression analysis showed that age, hypertension, diabetes, intracranial arterial stenosis, and total cerebral small vessel disease burden were independent risk factors. On the basis of each regression coefficient, a 10-point predictive scoring system selected the highest Jordon index as the cut-off value, which was 4 points. And the area under the receiver operating characteristic curve was 0.842 (95 %CI: 0.796~0.893, P＜0.001). Conclusions The predictive scoring system based on age, hypertension, diabetes, intracranial arterial stenosis, and total cerebral small vessel disease burden can effectively predict whether patients with cerebral small vessel disease are tend to be onset with twice or more strokes.

The Correlation Between Modified Total Cerebral Small Vessel Disease Score and Gait and Balance Disorder in Middle-aged to Older Adults.

The aim of this study is to investigate the relationships between the original and modified total cerebral Small Vessel Disease (CSVD) score and gait and balance impairment using quantitative and semi-quantitative tests. In our study, patients aged 45 to 85 consecutively recruited. CSVD manifestations were identified with brain Magnetic Resonance Imaging (MRI), and the original and modified CSVD scores were calculated based on the results. Gait and balance function were assessed using both gait parameters and clinical rating scales. The correlation between the original and modified total scores of the CSVD and gait and balance dysfunction was demonstrated. 224 patients were enrolled in the study. Gait and balance disorders were associated with both the original and modified CSVD scores. A significant association remained after adjusting for gender, height, age, hypertension, and other relevant risk factors. The binary logistic regression and chi-squared trend tests revealed that impairment of movement function significantly correlated with the modified CSVD score and that the dysfunction was significantly higher for patients with modified CSVD scores of 5-6 than those with scores of 1-2. In Receiver Operating Characteristic (ROC) analysis, modified CSVD scores were more accurate in predicting gait impairment than original CSVD scores. We found both original and modified total CSVD scores to be related to gait and balance disorder, and the modified CSVD score was more accurate in identifying movement impairment and should be used as an effective tool in investigating CSVD and motor dysfunction.

Relationship Between Plasma Lipopolysaccharides, Gut Microbiota, and Dementia: A Cross-Sectional Study

Previous studies have demonstrated associations between gut microbiota, microbial metabolites, and cognitive decline. However, relationships between these factors and lipopolysaccharides (LPS; molecules of the outer membrane of gram-negative bacteria) remain controversial. To evaluate associations between plasma LPS, gut microbiota, and cognitive function. We performed a cross-sectional sub-analysis of data of 127 participants (women: 58%, mean age: 76 years) from our prospective cohort study regarding the relationship between gut microbiota and cognitive function. We enrolled patients who visited our memory clinic and assessed demographics, dementia-related risk factors, cognitive function, brain imaging, gut microbiomes, and microbial metabolites. We evaluated relationships between cognitive decline and plasma LPS using multivariable logistic regression analyses. Plasma LPS concentration increased with increasing degree of cognitive decline and total cerebral small vessel disease (SVD) score (Kruskal-Wallis test; p = 0.016 and 0.007, respectively). Participants with high plasma LPS concentrations tended to have lower concentrations of gut microbial metabolites, such as lactic acid and acetic acid, and were less likely to consume fish and shellfish (44.7% versus 69.6%, p = 0.027) than those with low plasma LPS concentrations. Multivariable analyses revealed that plasma LPS concentration was independently associated with the presence of mild cognitive impairment in participants without dementia (odds ratio: 2.09, 95% confidence interval: 1.14-3.84, p = 0.007). In this preliminary study, plasma LPS concentration was associated with both cognitive decline and cerebral SVD and significantly correlated with beneficial gut microbial metabolites. Plasma LPS may be a risk factor for cognitive decline.

Total Cerebral Small Vessel Disease Score and Cerebral Bleeding Risk in Patients With Acute Stroke Treated With Intravenous Thrombolysis.

ObjectiveThe aim of this study was to investigate the association of total cerebral small vessel disease (cSVD) score with the risk of intracerebral hemorrhage (ICH) in patients with acute ischemic stroke who received intravenous thrombolysis (IVT) using recombinant tissue-plasminogen activator (rt-PA).MethodsWe retrospectively reviewed clinical data from two stroke registries of patients with acute ischemic stroke treated with IVT. We assessed the baseline magnetic resonance (MR) visible cSVD markers and total cSVD score (ranging from 0 to 4) between patients with and without ICH after IVT. Logistic regression analysis was used to determine the association of total cSVD score with the risk of ICH after IVT, adjusted for cofounders selected by least absolute shrinkage and selection operator (LASSO). We additionally performed an E-value analysis to fully explain away a specific exposure-outcome association. Receiver operating characteristic (ROC) curve analysis was used to quantify the predictive potential of the total cSVD score for any ICH after IVT.ResultsAmong 271 eligible patients, 55 (20.3%) patients experienced any ICH, 16 (5.9%) patients experienced a symptomatic ICH (sICH), and 5 (1.85%) patients had remote intracranial parenchymal hemorrhage (rPH). Logistic regression analysis showed that the risk of any ICH increased with increasing cSVD score [per unit increase, adjusted odds ratio (OR) 2.03, 95% CI 1.22–3.41, P = 0.007]. Sensitivity analyses using E-value revealed that it would need moderately robust unobserved confounding to render the exposure-outcome (cSVD-any ICH) association null. ROC analysis showed that compared with the National Institutes of Health Stroke Scale (NIHSS) score alone, a combination of cSVD and NIHSS score had a larger area under the curve for any ICH (0.811, 95% CI 0.756–0.866 vs. 0.784, 95% CI 0.723–0.846, P = 0.0004).ConclusionThe total cSVD score is associated with an increased risk of any ICH after IVT and improves prediction for any ICH compared with NIHSS alone.

White Matter Free Water Outperforms Cerebral Small Vessel Disease Total Score in Predicting Cognitive Decline in Persons with Mild Cognitive Impairment.

Vascular pathology is an important partner of Alzheimer's disease (AD). Both total cerebral small vessel disease (CSVD) score and white matter free water (FW) are useful markers that could reflect cerebral vascular injury. We aim to investigate the efficacy of these two metrics in predicting cognitive declines in patients with mild cognitive impairment (MCI). We enrolled 126 MCI subjects with 3D T1-weighted images, fluid-attenuated inversion recovery images, T2* images, diffusion tensor imaging images, cerebrospinal fluid biomarkers and neuropsychological tests from the Alzheimer's Disease Neuroimaging Initiative database. The total CSVD score and FW values were calculated. Simple and multiple linear regression analyses were applied to explore the association between vascular and cognitive impairments. Linear mixed effect models were constructed to investigate the efficacy of total CSVD score and FW on predicting cognitive decline. FW was associated with baseline cognition and could predict the decline of executive and language functions in MCI subjects, while no association was found between total CSVD score and cognitive declines. FW is a promising imaging marker for investigating the effect of CSVD on AD progression.

Association between periodic limb movements during sleep and neuroimaging features of cerebral small vessel disease: A preliminary cross-sectional study.

Evidence on the relationship between periodic limb movements during sleep (PLMS) and cerebral small vessel disease is lacking. This study aimed to assess the association between the PLMS index and the neuroimaging features of cerebral small vessel disease on magnetic resonance imaging. Consecutive patients diagnosed with cerebral small vessel disease were enrolled. Data on the clinical characteristics, polysomnography, and brain magnetic resonance imaging were collected. The Accubrain software was used to calculate automatically the volume of white matter hyperintensities, the number of lacunar infarctions, and cerebral microbleeds. The severity of white matter hyperintensities, enlarged basal ganglia perivascular spaces, and the total cerebral small vessel disease scores were also rated visually using semiquantitative scales. The severity of PLMS was measured using the PLMS index, and the patients were divided into two groups using an established cut-off value of ≥15 per hour. Logistic regression was used to examine the association between PLMS and the neuroimaging features of cerebral small vessel disease. In total, 37 patients were included in the final analyses. The mean age was 66.49±11.31years, and 73.0% were males. The mean PLMS index was 19.30±10.18. In univariate analyses, it was found that patients with cerebral small vessel disease with a PLMS index ≥15had increased enlarged basal ganglia perivascular spaces (OR 6.136, 95%CI 1.101-34.214) and increased total cerebral small vessel disease scores (OR 6.0, 95%CI 1.253-28.742). Only the association between the PLMS index and the total cerebral small vessel disease burden score remained statistically significant after adjusting for age, sex, and the presence of moderate to severe obstructive sleep apnea syndrome. In conclusion, an elevated PLMS index is likely to be associated with a greater cerebral small vessel disease burden. PLMS might be a novel potential marker of cerebral small vessel disease.

Macular Microvasculature Is Associated With Total Cerebral Small Vessel Disease Burden in Recent Single Subcortical Infarction.

PurposeTo assess the retinal microvasculature, choriocapillaris, and choroidal thickness in recent single subcortical infarction (RSSI) patients compared with healthy controls. We also assessed the correlation between the macular microvascular changes and choroidal changes with their clinical implications in RSSI patients.MethodsForty-six RSSI patients and 39 healthy controls (HC) were enrolled in our study. Magnetic resonance imaging (MRI) was done for all RSSI patients, and a total cerebral small vessel disease (CSVD) score was assessed for all patients. Swept-source optical coherence tomography (SS-OCT) was used to image and assess the choroidal thickness and SS-OCT angiography (SS-OCTA) was used to image and assess the macular microvasculature and choriocapillaris in all participants. Clinical information was collected for all participants.ResultsRSSI patients showed significantly sparser inner retinal microvasculature (P = 0.003) when compared with healthy controls. RSSI patients showed significantly thinner choroidal thickness (P < 0.001) when compared with HC. No significant difference (P = 0.247) was seen when the choriocapillaris was compared between the two groups. CSVD burden (P = 0.014) and NIHSS score (P = 0.010) showed significant correlation with the inner retinal microvasculature of RSSI patients. The inner retinal microvasculature (P = 0.016) and choroidal thickness (P = 0.018) showed a significant correlation with the MoCA scores in RSSI patients.ConclusionsOur report suggests that retinal and choroidal imaging may serve as useful indicators to expand our understanding of RSSI and its clinical validity.

Automated grading of enlarged perivascular spaces in clinical imaging data of an acute stroke cohort using an interpretable, 3D deep learning framework

Enlarged perivascular spaces (EPVS), specifically in stroke patients, has been shown to strongly correlate with other measures of small vessel disease and cognitive impairment at 1 year follow-up. Typical grading of EPVS is often challenging and time consuming and is usually based on a subjective visual rating scale. The purpose of the current study was to develop an interpretable, 3D neural network for grading enlarged perivascular spaces (EPVS) severity at the level of the basal ganglia using clinical-grade imaging in a heterogenous acute stroke cohort, in the context of total cerebral small vessel disease (CSVD) burden. T2-weighted images from a retrospective cohort of 262 acute stroke patients, collected in 2015 from 5 regional medical centers, were used for analyses. Patients were given a label of 0 for none-to-mild EPVS (< 10) and 1 for moderate-to-severe EPVS (≥ 10). A three-dimensional residual network of 152 layers (3D-ResNet-152) was created to predict EPVS severity and 3D gradient class activation mapping (3DGradCAM) was used for visual interpretation of results. Our model achieved an accuracy 0.897 and area-under-the-curve of 0.879 on a hold-out test set of 15% of the total cohort (n = 39). 3DGradCAM showed areas of focus that were in physiologically valid locations, including other prevalent areas for EPVS. These maps also suggested that distribution of class activation values is indicative of the confidence in the model’s decision. Potential clinical implications of our results include: (1) support for feasibility of automated of EPVS scoring using clinical-grade neuroimaging data, potentially alleviating rater subjectivity and improving confidence of visual rating scales, and (2) demonstration that explainable models are critical for clinical translation.